Interleukin 1 (IL-1) production is not essential for acquired resistance of human A375 melanoma cells to anti-proliferative effect of IL-1

✍ Scribed by Saotomo Itoh; Hidetoshi Hayashi; Naoko Watanabe; Yoshiro Kobayashi; Takemasa Takii; Kikuo Onozaki

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: French
• Weight: 817 KB
• Volume: 65
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19960315)65:6<805::aid-ijc17>3.0.co;2-2

✦ Synopsis

FOR ACQUIRED RESISTANCE OF HUMAN A375 MELANOMA

The proliferation of human melanoma cell line A375-6 is inhibited by interleukin I (IL-I). However, the cells acquired resistance to IL-I after a long period of culture. We have reported that 2 resistant subclones, A375-R8 and -R19, produced ILla constitutively and that IL-I induced IL-6 production in an autocrine manner. Therefore, we supposed that IL-la production renders the cells resistant to IL-I. To investigate the relationship between ILla production and IL-I resistance, we transfected the IL-I a expression plasmid to the IL-I -sensitive clone, A375-6, and the anti-sense mRNA expression plasmid to IL-I-resistant cells, A375-R8 and -R19. A375-6MS, a transfectant of mature IL-la expression plasmid, expressed IL-la mRNA and produced IL-I activity at a level comparable to the resistant cells. The transfectant also produced IL-6 and exhibited augmented expression of Mn-SOD mRNA. However, IL-I sensitivity of this transfectant was not affected. With respect to sensitivity to anti-proliferative effects of other cytokines, such as IL-6 and TNFa, there was no difference between the transfectant and parent cells. Although A375-R8PH I 0 and -R19PH 10, transfectants of ILla anti-sense mRNA expression plasmid, exhibited a decrease in the level of IL-l production, their IL-I sensitivity did not differ from parent cells. These results, therefore, suggest that ILla production is not essential or suffkient for the acquisition of resistance to the antiproliferative effect of IL-I.